DESCRIPTION: The goal of these studies is to use an unusual SIVmac239 variant (EvT3) to determine how useage of the CXCR4 co-receptor impacts on the rate of CD4+ T-cell decline in SIV-infected macaques. The first specific aim is to identify what co-receptors are used by EvT3 in vitro. The second is to determine the significance of co-receptor useage for the infection of CD4+ T-cell subsets by SIV. In the third specific aim, the genetic determinants in the gp120 glycoprotein that influence CXCR4 useage in vitro and CD4 depletion efficiency in vivo will be investigated. Specific aim 4 is to determine the significance of CD4+ T-cell activation for co-receptor expression and pathogenic effects.